Chovan Linda E, Black-Schaefer Candace, Dandliker Peter J, Lau Yau Yi
Global Pharmaceutical Research and Development, Abbott Laboratories, Advanced Technologies, Dept. R4CP, Bldg. AP52-N, 200 Abbott Park Road, Abbott Park, IL 60064-6217, USA.
Rapid Commun Mass Spectrom. 2004;18(24):3105-12. doi: 10.1002/rcm.1735.
High-throughput metabolic screening has been requested routinely to keep pace with high-throughput organic synthesis. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) with a fast gradient has become the method of choice for the task due to its sensitivity and selectivity. We have developed an automated system that consists of a robotic system for in vitro incubation and a commercially available software package for automatic MS/MS method development. A short, generic LC gradient and MS conditions that are applicable to most compounds have been developed to minimize the method development time and data analysis. This system has been used to support a number of in vitro screening assays in early drug discovery phase including microsomal stability and protein binding.
为了跟上高通量有机合成的步伐，常规需要进行高通量代谢筛选。具有快速梯度的液相色谱/串联质谱（LC/MS/MS）因其灵敏度和选择性已成为该任务的首选方法。我们开发了一个自动化系统，该系统由用于体外孵育的机器人系统和用于自动MS/MS方法开发的商业软件包组成。已经开发出一种适用于大多数化合物的简短通用LC梯度和MS条件，以尽量减少方法开发时间和数据分析。该系统已用于支持早期药物发现阶段的多项体外筛选试验，包括微粒体稳定性和蛋白结合试验。
